Article

The effects of short-term nicotine administration on behavioral and oxidative stress deficiencies induced in a rat model of Parkinson's disease.

"Alexandru Ioan Cuza" University, Deptartment of Biology, B dul Carol I, 11, 700506, Iasi, Romania.
Psychiatria Danubina (Impact Factor: 0.63). 06/2012; 24(2):194-205.
Source: PubMed

ABSTRACT We previously demonstrated that a 6-hydroxydopamine (6-OHDA) induced lesion of substantia nigra (SN), which is a very well known animal model of Parkinson's disease, resulted in memory deficits and increased brain oxidative stress. Also, recent reports had suggested that nicotine from smoke may contribute, at least in some parts, to the apparent neuroprotective effect of tobacco use in Parkinson's disease.
In this way, in the present study we were interested to examine the effects of low-dose nicotine administration (5 days, 0.3 mg/kg/day) in a rat model of Parkinson's disease, on behavioral parameters from Y-maze or shuttle-box task and also on the oxidative stress markers from the temporal lobe, which is one of the most vulnerable cortical area to oxidative stress effects.
The administration of nicotine resulted in significant improvements of short-term memory, as seen in the Y-maze task, as well an increase of conditioned avoidance responses and decreased number of escape failures in the shuttle-box task. Additionally, an increase in the specific activity of glutathione peroxidase and a decrease of the lipid peroxidation processes is reported. Moreover, we found a significant correlation between the behavioral results from the Y-maze and shuttle-box tasks and the levels of oxidative stress markers.
Taken together our data suggest that short-term administration of low-dose nicotine facilitates memory processes and improves the oxidative stress status of the brain, after a 6-OHDA induced lesion of the SN.

0 Bookmarks
 · 
137 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.
    Journal of the American Society for Experimental NeuroTherapeutics 10/2013; · 5.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Increased depression, somatization, gut inflammation and wider peripheral inflammation are all associated with the early stages of Parkinson's disease (PD). Classically such concurrent conditions have been viewed as "comorbidities", driven by high levels of stress in a still poorly understood and treated disorder. Here we review the data on how oxidative and nitrosative stress in association with immuno-inflammatory responses, drives alteration in tryptophan catabolites, including kynurenine, kynurenic acid and quinolinic acid that drive not only the "comorbidities" of PD but also important processes in the etiology and course of PD per se. The induction of indoleamine 2,3-dioxygenase, leading to the driving of tryptophan into neuroregulatory tryptophan catabolite products and away from serotonin and melatonin production, has significant implications for understanding the role of nicotine, melatonin, and caffeine in regulating PD susceptibility. Tryptophan catabolite pathway activation will also regulate blood-brain barrier permeability, glia and mast cell reactivity as well as wider innate and adaptive immune cell responses, all relevant to the course of PD. As such, the "comorbidities" of PD such as depression, somatization and peripheral inflammatory disorders can all be conceptualized as being an intricate part of the biological underpinnings of both the etiology and course of PD. As a consequence, the data reviewed here has treatment implications; relevant to both the course of PD and in the management of L-DOPA induced dyskinesias.
    CNS & neurological disorders drug targets 07/2013; · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD), the second most common neurodegenerative disease, impairs motor skills and cognitive function. To date, the drugs used for PD treatment provide only symptomatic relief. The identification of new drugs that show benefit in slowing the decline seen in PD patients is the focus of much current research. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana, a traditional Chinese medical herb. It has been shown to have anti-inflammatory properties, but no studies have yet described the effects of acetylcorynoline on PD. The aim of this study was to evaluate the potential for acetylcorynoline to improve PD in C. elegans models. In the present study, we used a pharmacological strain (BZ555) that expresses green fluorescent protein specifically in dopaminergic neurons, and a transgenic strain (OW13) that expresses human α-synuclein in muscle cells to study the antiparkinsonian effects of acetylcorynoline. Our experimental data showed that treatment with up to 10 mM acetylcorynoline does not cause toxicity in animals. Acetylcorynoline significantly decreases dopaminergic neuron degeneration induced by 6-hydroxydopamine in BZ555 strain; prevents α-synuclein aggregation; recovers lipid content in OW13 strain; restores food-sensing behavior, and dopamine levels; and prolongs life-span in 6-hydroxydopamine-treated N2 strain, thus showing its potential as a possible antiparkinsonian drug. Acetylcorynoline may exert its effects by decreasing egl-1 expression to suppress apoptosis pathways and by increasing rpn5 expression to enhance the activity of proteasomes.
    Neuropharmacology 08/2013; · 4.11 Impact Factor

Similar Publications